The major objectives of this project are to elucidate the roles of viral macromolecules in the replication of viruses and regulation of host processes. A long range goal is to evaluate specific viral functions as targets of antiviral agents. Current studies are focused on the structure, synthesis, modification, and function of messenger RNA (mRNA). We found that both viral and cellular mRNAs contain a sequence of methylated nucleotides at their 5'-terminals, i.e. that end of the the mRNA that binds to ribosomes for translation, as well as at internal locations. In the case of vaccinia virus, the mRNA modification enzymes have been isolated and the steps involved in the formation of the 5'-terminal structure have been determined. Similar work on the modification of cellular mRNAs is in progress. We anticipate that continuation of these studies will further our understanding of the synthesis and processing of viral and cellular mRNAs. The possibility that regulation of viral or cellular protein synthesis is mediated by the modification of mRNA is under investigation.